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A comprehensive review on organ-on-chips as powerful preclinical models to study tissue barriers 器官芯片作为研究组织屏障的强大临床前模型的全面综述
Pub Date : 2024-09-15 DOI: 10.1088/2516-1091/ad776c
Yagmur Filiz, Alessio Esposito, Carmelo De Maria, Giovanni Vozzi and Ozlem Yesil-Celiktas
In the preclinical stage of drug development, 2D and 3D cell cultures under static conditions followed by animal models are utilized. However, these models are insufficient to recapitulate the complexity of human physiology. With the developing organ-on-chip (OoC) technology in recent years, human physiology and pathophysiology can be modeled better than traditional models. In this review, the need for OoC platforms is discussed and evaluated from both biological and engineering perspectives. The cellular and extracellular matrix components are discussed from a biological perspective, whereas the technical aspects such as the intricate working principles of these systems, the pivotal role played by flow dynamics and sensor integration within OoCs are elucidated from an engineering perspective. Combining these two perspectives, bioengineering applications are critically discussed with a focus on tissue barriers such as blood-brain barrier, ocular barrier, nasal barrier, pulmonary barrier and gastrointestinal barrier, featuring recent examples from the literature. Furthermore, this review offers insights into the practical utility of OoC platforms for modeling tissue barriers, showcasing their potential and drawbacks while providing future projections for innovative technologies.
在药物开发的临床前阶段,人们利用静态条件下的二维和三维细胞培养物以及动物模型。然而,这些模型不足以再现人体生理的复杂性。近年来,随着片上器官(OoC)技术的发展,人体生理和病理生理学的建模效果比传统模型更好。本综述将从生物学和工程学的角度讨论和评估 OoC 平台的需求。从生物学的角度讨论了细胞和细胞外基质的成分,而从工程学的角度阐明了这些系统复杂的工作原理、流动动力学所起的关键作用以及 OoCs 中的传感器集成等技术方面的问题。结合这两个视角,本综述对生物工程应用进行了批判性讨论,重点关注血脑屏障、眼屏障、鼻屏障、肺屏障和胃肠道屏障等组织屏障,并列举了最新的文献实例。此外,本综述还深入探讨了 OoC 平台在组织屏障建模中的实际效用,展示了其潜力和缺点,并对创新技术的未来进行了预测。
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引用次数: 0
Biomedical prospects and challenges of metal dichalcogenides nanomaterials 二卤化金属纳米材料的生物医学前景与挑战
Pub Date : 2024-08-13 DOI: 10.1088/2516-1091/ad6abb
Preeti Goswami, Videsh Kumar, Govind Gupta
The biomedical applications of metal dichalcogenides (MDCs) nanomaterials (NMs) are an emerging discipline because of their unique attributes like high surface-to-volume ratio, defect sites, superb catalytic performance, and excitation-dependent emission, which is helpful in bio-imaging and cancer cell killing. Due to the compatibility of sensing material with cells and tissues, MoS2, WS2, and SnS2 NMs have piqued the interest of researchers in various biomedical applications like photothermal therapy used in killing cancer cells, drug delivery, photoacoustic tomography (PAT) used in bio-imaging, nucleic acid or gene delivery, tissue engineering, wound healing, etc. Furthermore, these NMs’ functionalization and defect engineering can enhance therapeutic efficacy, biocompatibility, high drug transport efficiency, adjustable drug release, dispersibility, and biodegradability. Among the aforementioned materials, MoS2 NMs have extensively been explored via functionalization and defects engineering to improve biosensing properties. However, further enhancement is still available. Aside from MoS2, the distinct chemo-physical and optical features of WS2 and SnS2 NMs promise considerable potential in biosensing, nanomedicine, and pharmaceuticals. This article mainly focuses on the challenges and future aspects of two-dimensional MDCs NMs in biomedical applications, along with their advancements in various medical diagnosis processes.
金属二卤化物(MDCs)纳米材料(NMs)的生物医学应用是一门新兴学科,因为它们具有独特的属性,如高表面体积比、缺陷位点、超强的催化性能和依赖激发的发射,有助于生物成像和癌细胞杀伤。由于传感材料与细胞和组织的相容性,MoS2、WS2 和 SnS2 NMs 在各种生物医学应用中引起了研究人员的兴趣,如用于杀死癌细胞的光热疗法、药物输送、用于生物成像的光声断层扫描(PAT)、核酸或基因输送、组织工程、伤口愈合等。此外,这些非金属材料的功能化和缺陷工程可以提高疗效、生物相容性、高药物传输效率、可调药物释放、分散性和生物降解性。在上述材料中,通过功能化和缺陷工程改善生物传感性能的 MoS2 NMs 已得到广泛探索。不过,它们的性能还有待进一步提高。除 MoS2 外,WS2 和 SnS2 NMs 也具有独特的化学物理和光学特性,有望在生物传感、纳米医学和制药领域大显身手。本文主要关注二维 MDCs 纳米金属在生物医学应用中面临的挑战和未来发展方向,以及它们在各种医疗诊断过程中的应用进展。
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引用次数: 0
The adult large bowel: describing environment morphology for effective biomedical device development 成人大肠:描述环境形态以有效开发生物医学设备
Pub Date : 2024-08-09 DOI: 10.1088/2516-1091/ad6dbf
J. Norton, James W. Martin, Conchubhair Winters, Bruno Scaglioni, K. Obstein, Venkataraman Subramanian, Pietro Valdastri
An understanding of the biological environment, and in particular the physical morphology, is crucial for those developing medical devices and software applications. It not only informs appropriate design inputs, but provides the opportunity to evaluate outputs via virtual or synthetic models before investing in costly clinical investigations. The large bowel is a pertinent example, having a major demand for effective technological solutions to clinical unmet needs. Despite numerous efforts in this area, there remains a paucity of accurate and reliable data in literature. This work reviews what is available, including both processed datasets and raw medical images, before providing a comprehensive quantitative description of the environment for biomedical engineers in this and related regions of the body. CT images from 75 patients, and a blend of different mathematical and computational methods, are used to calculate and define several crucial metrics, including: a typical adult size (abdominal girth) and abdominal shape, location (or depth) of the bowel inside the abdomen, large bowel length, lumen diameter, flexure number and characteristics, volume and anatomical tortuosity. These metrics are reviewed and defined by both gender and body posture, as well as – wherever possible – being spilt into the various anatomical regions of the large bowel. The resulting data can be used to describe a realistic “average” adult large bowel environment and so drive both design specifications and high fidelity test environments.
了解生物环境,尤其是物理形态,对于开发医疗设备和软件应用程序至关重要。它不仅为适当的设计输入提供信息,还提供了在投入昂贵的临床研究之前通过虚拟或合成模型评估输出结果的机会。大肠就是一个相关的例子,它对有效的技术解决方案有着重大需求,以满足临床未满足的需求。尽管在这一领域做出了许多努力,但准确可靠的文献数据仍然很少。这项工作回顾了现有的数据,包括处理过的数据集和原始医学图像,然后为生物医学工程师全面定量描述了人体这一区域和相关区域的环境。来自 75 名患者的 CT 图像以及不同的数学和计算方法被用来计算和定义几个关键指标,包括:典型的成人体型(腹围)和腹部形状、肠道在腹腔内的位置(或深度)、大肠长度、管腔直径、挠曲数量和特征、体积和解剖迂曲度。这些指标按性别和体态进行审查和定义,并尽可能按大肠的不同解剖区域进行划分。由此得出的数据可用于描述现实的 "平均 "成人大肠环境,从而推动设计规范和高保真测试环境的发展。
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引用次数: 0
Advances in antimicrobial orthopaedic devices and FDA regulatory challenges 抗菌矫形器械的发展和美国食品及药物管理局的监管挑战
Pub Date : 2024-08-01 DOI: 10.1088/2516-1091/ad5cb1
Mehdi Kazemzadeh-Narbat, Asija Memic, Kevin B McGowan, Adnan Memic and Ali Tamayol
Implant-associated infections, caused by the formation of biofilms especially antibiotic resistant organisms, are among the leading causes of orthopaedic implant failure. Current strategies to combat infection and biofilm focus on either inhibiting bacterial growth or preventing bacterial adherence that could lead to biofilm creation. Despite research on developing numerous antimicrobial orthopaedic devices, to date, no robust solution has been translated to the clinic. One of the key bottlenecks is the disconnect between researchers and regulatory agencies. In this review, we outline recent strategies for minimizing orthopaedic implant-associated infections. In addition, we discuss the relevant Food and Drug Administration regulatory perspectives, challenges. We also highlight emerging technologies and the directions the field that is expected to expand. We discuss in depth challenges that include identifying strategies that render implants antibacterial permanently or for a long period of time without the use of antimicrobial compounds that could generate resistance in pathogens and negatively impact osseointegration.
由生物膜(尤其是抗生素耐药菌)形成引起的植入物相关感染是骨科植入物失效的主要原因之一。目前抗感染和生物膜的策略主要是抑制细菌生长或防止细菌附着导致生物膜的形成。尽管研究人员开发了许多抗菌骨科设备,但迄今为止,还没有一种可靠的解决方案被应用于临床。其中一个关键瓶颈是研究人员与监管机构之间的脱节。在这篇综述中,我们概述了尽量减少骨科植入物相关感染的最新策略。此外,我们还讨论了食品药品管理局的相关监管观点和挑战。我们还强调了新兴技术以及该领域有望扩展的方向。我们深入探讨了面临的挑战,其中包括确定可使植入物永久抗菌或长期抗菌的策略,而无需使用可能使病原体产生抗药性并对骨结合产生负面影响的抗菌化合物。
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引用次数: 0
Tackling the small data problem in medical image classification with artificial intelligence: a systematic review 用人工智能解决医学影像分类中的小数据问题:系统综述
Pub Date : 2024-06-16 DOI: 10.1088/2516-1091/ad525b
Stefano Piffer, Leonardo Ubaldi, Sabina Tangaro, Alessandra Retico and Cinzia Talamonti
Though medical imaging has seen a growing interest in AI research, training models require a large amount of data. In this domain, there are limited sets of data available as collecting new data is either not feasible or requires burdensome resources. Researchers are facing with the problem of small datasets and have to apply tricks to fight overfitting. 147 peer-reviewed articles were retrieved from PubMed, published in English, up until 31 July 2022 and articles were assessed by two independent reviewers. We followed the Preferred Reporting Items for Systematic reviews and Meta-Analyse (PRISMA) guidelines for the paper selection and 77 studies were regarded as eligible for the scope of this review. Adherence to reporting standards was assessed by using TRIPOD statement (transparent reporting of a multivariable prediction model for individual prognosis or diagnosis). To solve the small data issue transfer learning technique, basic data augmentation and generative adversarial network were applied in 75%, 69% and 14% of cases, respectively. More than 60% of the authors performed a binary classification given the data scarcity and the difficulty of the tasks. Concerning generalizability, only four studies explicitly stated an external validation of the developed model was carried out. Full access to all datasets and code was severely limited (unavailable in more than 80% of studies). Adherence to reporting standards was suboptimal (<50% adherence for 13 of 37 TRIPOD items). The goal of this review is to provide a comprehensive survey of recent advancements in dealing with small medical images samples size. Transparency and improve quality in publications as well as follow existing reporting standards are also supported.
虽然医学影像领域对人工智能研究的兴趣与日俱增,但训练模型需要大量数据。在这一领域,可用的数据集有限,因为收集新数据要么不可行,要么需要耗费大量资源。研究人员面临着数据集较小的问题,不得不采用一些技巧来对抗过度拟合。我们从 PubMed 上检索了截至 2022 年 7 月 31 日以英文发表的 147 篇同行评审文章,并由两名独立评审员对文章进行了评估。我们遵循系统综述和元分析首选报告项目(PRISMA)指南进行论文筛选,77 项研究被认为符合本综述的范围。我们使用 TRIPOD 声明(针对个体预后或诊断的多变量预测模型的透明报告)对报告标准的遵守情况进行了评估。为解决小数据问题,分别有75%、69%和14%的病例采用了迁移学习技术、基本数据增强技术和生成对抗网络。考虑到数据的稀缺性和任务的难度,60% 以上的作者进行了二元分类。关于可推广性,只有四项研究明确指出对所开发的模型进行了外部验证。对所有数据集和代码的全面访问受到严重限制(超过 80% 的研究无法获得)。对报告标准的遵守情况不尽如人意(37 个 TRIPOD 项目中有 13 个项目的遵守率低于 50%)。本综述的目的是对处理小样本医学影像的最新进展进行全面调查。同时还支持提高出版物的透明度和质量,以及遵循现有的报告标准。
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引用次数: 0
Ultrasound Imaging based recognition of prenatal anomalies: A systematic clinical engineeringreview 基于超声成像的产前畸形识别:系统性临床工程回顾
Pub Date : 2024-04-03 DOI: 10.1088/2516-1091/ad3a4b
N. Sriraam, Babu Chinta, S. Suresh, Suresh Sudarshan
For prenatal screening, ultrasound imaging allows for real-time observation of developing fetal anatomy. Understanding normal and aberrant forms through extensive fetal structural assessment enables for early detection and intervention. However, the reliability of anomaly diagnosis varies depending on operator expertise and device limits. First trimester scans in conjunction with circulating biochemical markers are critical in identifying high-risk pregnancies, but they also pose technical challenges. Recent engineering advancements in automated diagnosis, such as AI-based ultrasound image processing and multimodal data fusion, are developing to improve screening efficiency, accuracy, and consistency. Still, creating trust in these data-driven solutions is necessary for integration and acceptability in clinical settings. Transparency can be promoted by explainable AI (XAI) technologies that provide visual interpretations and illustrate the underlying diagnostic decision making process. An explanatory framework based on deep learning is suggested to construct charts depicting anomaly screening results from ultrasound video feeds. AI modeling can then be applied to these charts to connect defects with probable deformations. Overall, engineering approaches that increase imaging, automation, and interpretability hold enormous promise for altering traditional workflows and expanding diagnostic capabilities for better prenatal care.
在产前筛查方面,超声成像可实时观察胎儿的发育解剖结构。通过广泛的胎儿结构评估,了解正常和异常胎儿的形态,以便及早发现和干预。然而,异常诊断的可靠性因操作者的专业知识和设备限制而异。怀孕头三个月的扫描与循环生化标记物相结合,对识别高危妊娠至关重要,但也带来了技术挑战。最近在自动诊断方面取得的工程技术进步,如基于人工智能的超声图像处理和多模态数据融合,正在提高筛查效率、准确性和一致性。不过,要在临床环境中实现整合和可接受性,就必须建立对这些数据驱动解决方案的信任。可解释的人工智能(XAI)技术可提供可视化解释并说明基本诊断决策过程,从而提高透明度。建议采用基于深度学习的解释框架来构建图表,描述超声波视频馈送的异常筛查结果。然后,可将人工智能建模应用于这些图表,将缺陷与可能的变形联系起来。总之,提高成像、自动化和可解释性的工程方法在改变传统工作流程和扩展诊断能力以改善产前护理方面大有可为。
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引用次数: 0
Trends and advances in silk based 3D printing/bioprinting towards cartilage tissue engineering and regeneration 丝基三维打印/生物打印在软骨组织工程和再生方面的趋势和进展
Pub Date : 2024-03-21 DOI: 10.1088/2516-1091/ad2d59
Yogendra Pratap Singh, Ashutosh Bandyopadhyay, Souradeep Dey, Nandana Bhardwaj, Biman B Mandal
Cartilage repair remains a significant clinical challenge in orthopedics due to its limited self- regeneration potential and often progresses to osteoarthritis which reduces the quality of life. 3D printing/bioprinting has received vast attention in biofabrication of functional tissue substitutes due to its ability to develop complex structures such as zonally structured cartilage and osteochondral tissue as per patient specifications with precise biomimetic control. Towards a suitable bioink development for 3D printing/bioprinting, silk fibroin has garnered much attention due to its advantageous characteristics such as shear thinning behavior, cytocompatibility, good printability, structural fidelity, affordability, and ease of availability and processing. This review attempts to provide an overview of current trends/strategies and recent advancements in utilizing silk-based bioinks/biomaterial-inks for cartilage bioprinting. Herein, the development of silk-based bioinks/biomaterial-inks, its components and the associated challenges, along with different bioprinting techniques have been elaborated and reviewed. Furthermore, the applications of silk-based bioinks/biomaterial-inks in cartilage repair followed by challenges and future directions are discussed towards its clinical translations and production of next-generation biological implants.
由于软骨的自我再生潜力有限,软骨修复仍是骨科领域的一项重大临床挑战,而且往往会发展为骨关节炎,降低生活质量。三维打印/生物打印技术在功能性组织替代物的生物制造方面受到了广泛关注,因为它能够根据患者的具体要求,通过精确的生物仿真控制,制造出复杂的结构,如分区结构软骨和骨软骨组织。为了开发适合三维打印/生物打印的生物墨水,蚕丝纤维素因其剪切稀化行为、细胞相容性、良好的可打印性、结构保真度、经济实惠、易于获得和加工等优势特性而备受关注。本综述试图概述利用丝基生物墨水/生物材料墨水进行软骨生物打印的当前趋势/策略和最新进展。本文阐述并综述了丝基生物墨水/生物材料墨水的发展、其成分和相关挑战,以及不同的生物打印技术。此外,还讨论了丝基生物墨水/生物材料墨水在软骨修复中的应用,以及在临床应用和生产下一代生物植入物方面所面临的挑战和未来发展方向。
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引用次数: 0
Combining simulation models and machine learning in healthcare management: Strategies and applications 在医疗保健管理中结合模拟模型和机器学习:策略与应用
Pub Date : 2024-01-24 DOI: 10.1088/2516-1091/ad225a
A. M. Ponsiglione, P. Zaffino, C. Ricciardi, Danilo Di Laura, M. Spadea, Gianmaria De Tommasi, G. Improta, Maria Romano, Francesco Amato
Simulation models and artificial intelligence are largely used to address healthcare and biomedical engineering problems. Both approaches showed promising results in the analysis and optimization of healthcare processes. Therefore, the combination of simulation models and artificial intelligence could provide a strategy to further boost the quality of health services. In this work, a systematic review of studies applying a hybrid simulation models and artificial intelligence approach to address healthcare management challenges was carried out. Scopus, Web of Science, and PubMed databases were screened by independent reviewers. The main strategies to combine simulation and artificial intelligence as well as the major healthcare application scenarios were identified and discussed. Moreover, tools and algorithms to implement the proposed approaches were described. Results showed that machine learning appears to be the most employed artificial intelligence strategy in combination with simulation models, which mainly rely on agent-based and discrete-event systems. The scarcity and heterogeneity of the included studies suggested that a standardized framework to implement hybrid machine learning-simulation approaches in healthcare management is yet to be defined. Future efforts should aim to use these approaches to design novel intelligent in-silico models of healthcare processes and to provide effective translation to the clinics.
仿真模型和人工智能在很大程度上被用于解决医疗保健和生物医学工程问题。这两种方法在分析和优化医疗保健流程方面都取得了可喜的成果。因此,仿真模型与人工智能的结合可以为进一步提高医疗服务质量提供一种策略。在这项工作中,我们对应用仿真模型和人工智能混合方法应对医疗保健管理挑战的研究进行了系统综述。独立审稿人对 Scopus、Web of Science 和 PubMed 数据库进行了筛选。确定并讨论了仿真与人工智能相结合的主要策略以及主要的医疗应用场景。此外,还介绍了实施建议方法的工具和算法。结果表明,机器学习似乎是与仿真模型结合使用最多的人工智能策略,而仿真模型主要依赖于基于代理的系统和离散事件系统。所纳入研究的稀缺性和异质性表明,在医疗保健管理中实施机器学习-模拟混合方法的标准化框架尚未确定。未来的工作目标应该是利用这些方法为医疗保健流程设计新颖的智能内嵌模型,并将其有效地应用于临床。
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引用次数: 0
Antibiofilm approaches as a new paradigm for treating infections 抗生物膜方法是治疗感染的新模式
Pub Date : 2024-01-09 DOI: 10.1088/2516-1091/ad1cd6
F. Reffuveille, Yasser Dghoughi, M. Colin, M. Torres, C. de la Fuente-Nunez
The lack of effective antibiotics for drug-resistant infections has led the World Health Organization (WHO) to declare antibiotic resistance a global priority. Most bacterial infections are caused by microbes growing in structured communities called biofilms. Bacteria growing in biofilms are less susceptible to antibiotics than their planktonic counterparts. Despite their significant clinical implications, bacterial biofilms have not received the attention they warrant, with no approved antibiotics specifically designed for their eradication. In this paper, we aim to shed light on recent advancements in antibiofilm strategies that offer compelling alternatives to traditional antibiotics. Additionally, we will briefly explore the potential synergy between computational approaches, including the emerging field of artificial intelligence, and the accelerated design and discovery of novel antibiofilm molecules in the years ahead.
由于缺乏有效的抗生素来治疗耐药性感染,世界卫生组织(WHO)宣布将抗生素耐药性问题列为全球优先事项。大多数细菌感染是由生长在称为生物膜的结构化群落中的微生物引起的。与浮游生物相比,生长在生物膜中的细菌对抗生素的敏感性较低。尽管细菌生物膜对临床有重大影响,但却没有得到应有的重视,也没有专门用于根除生物膜的抗生素获得批准。本文旨在介绍抗生物膜策略的最新进展,这些策略为传统抗生素提供了令人信服的替代品。此外,我们还将简要探讨计算方法(包括新兴的人工智能领域)与加速设计和发现新型抗生物膜分子之间的潜在协同作用。
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引用次数: 0
Bioprinted in vitro tissue models: an emerging platform for developing therapeutic interventions and disease modelling 生物打印体外组织模型:开发治疗干预和疾病建模的新兴平台
Pub Date : 2023-12-14 DOI: 10.1088/2516-1091/ad10b4
Nandana Bhardwaj, Souradeep Dey, Bibrita Bhar, Biman B Mandal
In the past decade, the use of three-dimensional (3D) bioprinting technology for the development of in vitro tissue models has attracted a great deal of attention. This is due to its remarkable precision in constructing different functional tissues and organs, enabling studies of their biology. In addition, this high-throughput technology has been extended to therapeutics, as it provides an alternative functional platform for rapid drug screening and disease modelling. Functional tissue models fabricated using 3D bioprinting mimic native tissues and help in the development of platforms for personalized drug screening and disease modelling due to their high throughput and ease of customization. Moreover, bioprinted 3D tissue models mimic native tissues more closely and provide added advantages over earlier conventional tissue models, such as monoculture, co-culture, explants, etc. In this context, this review article provides an overview of different bioprinted in vitro tissue models of skin, bone, neural tissue, vascular tissue, cartilage, liver and cardiac tissue. This article explores advancements and innovations in these models in terms of developing improved therapeutic interventions. Herein, we provide an insight into the development of different bioprinted tissue models for applications in drug screening and disease modelling. The needs and advantages of bioprinted tissue models as compared with conventional in vitro models are discussed. Furthermore, the different biomaterials, cell sources and bioprinting techniques used to develop tissue models are briefly reviewed. Thereafter, different bioprinted tissue models, namely skin, liver, vascular, cardiac, cartilage, bone and neural tissue, are discussed in detail with a special emphasis on drug screening and disease modelling. Finally, challenges and future prospects are highlighted and discussed. Taken together, this review highlights the different approaches and strategies used for the development of different 3D bioprinted in vitro tissue models for improved therapeutic interventions.
在过去十年中,利用三维(3D)生物打印技术开发体外组织模型引起了广泛关注。这得益于三维生物打印技术在构建不同功能组织和器官方面的卓越精确性,从而能够对其生物学特性进行研究。此外,这种高通量技术还被扩展到治疗领域,因为它为快速药物筛选和疾病建模提供了另一种功能平台。利用三维生物打印技术制作的功能组织模型可模仿原生组织,由于其高通量和易于定制,有助于开发个性化药物筛选和疾病建模平台。此外,生物打印三维组织模型更接近原生组织,与早期的单培养、共培养、外植体等传统组织模型相比具有更多优势。在此背景下,这篇综述文章概述了皮肤、骨骼、神经组织、血管组织、软骨、肝脏和心脏组织等不同的生物打印体外组织模型。本文探讨了这些模型在改进治疗干预方面的进步和创新。在此,我们将深入探讨不同生物打印组织模型在药物筛选和疾病建模中的应用。与传统的体外模型相比,我们讨论了生物打印组织模型的需求和优势。此外,还简要回顾了用于开发组织模型的不同生物材料、细胞来源和生物打印技术。随后,详细讨论了不同的生物打印组织模型,即皮肤、肝脏、血管、心脏、软骨、骨骼和神经组织,并特别强调了药物筛选和疾病建模。最后,重点讨论了面临的挑战和未来前景。综上所述,本综述重点介绍了用于开发不同三维生物打印体外组织模型的不同方法和策略,以改进治疗干预措施。
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引用次数: 0
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